Accurate, early disease diagnosis and monitoring are critical aspects to effective prevention, treatment, and remission of disease. Most diagnostic methods available today are not simple or sensitive enough to significantly impact patients' response to treatment or survival outcome. This unmet need is highlighted by diseases, such as brain cancers, that often remain asymptomatic at early stages and then grow aggressively- with fast, fatal outcomes. We have invented immunosignatures (IS) as a new approach to disease diagnoses that addresses these problems. IS is based on querying blood-serum. Using antibodies as biomarkers of disease takes advantage of a stable and easily accessible molecule and the immune system's convenient properties of diversity, surveillance, and biological amplification. The complexity of a mammalian immune system is staggering and therefore so is the information content. The reductions in cost, elimination of surgery, imaging, and the simplicity of this rapid assay pave the way to frequent, accurate monitoring of individuals in remission and those in trials with new therapies. The innovative program presented here will build IS into a rapid, accurate diagnostic tool and demonstrate its effectiveness for brain cancer. In phase I we will validate the power of HealthTell's platform to identify peptide mimotopes (selected from a library of 330,000 random sequences) that accurately diagnose gliomas from other cancers, and classify them relative their pathological types and grades, and molecular subtypes. These will be rigorously explored and expanded in phase II to include analyses of additionally important groups: the lower grade primary gliomas and secondary brain cancers such as metastatic lung and breast cancers. Inclusion of sera from healthy volunteers in geographically matched sites relative to patients and additional blinded cohorts studies will provide data for high level performance metrics to be established. Within the term of this program, the peptide signatures will facilitate remission-stage and treatment monitoring, enabling more effective management of gliomas including better modulation of chemotherapy and radiation, and faster, more accurate evaluations of new targeted therapies. We intend to partner with the CAP/CLIA certified DNA Diagnostics Laboratory situated on the St. Joseph's Hospital Medical Center/Barrows Neurological Institute (BNI) campus for commercialization and validation relative to conventional diagnostics. Combined with the fact that BNI sees more brain tumor patients than any other place in the US, we are strongly positioned for moving this diagnostic product quickly into clinical use. Beyond this program, the peptide biomarkers identified and validated in this program will serve as early stage watch-dogs for new brain cancers on a single, universal health chip. This aligns with HealthTell's business plan of commercializing a simple, inexpensive microchip to monitor asymptomatic people for early development of disease. Continuous monitoring of healthy people would permit perturbations, such as brain cancer signatures, to be detected early.